Figure 7. Scheme illustrating activation of p40phox in AMs and its inhibition by PGE₂.

NADPHox is formed by a catalytic core (p22phox and gp91phox), present at the membrane, and the cytosolic subunits (p67phox, p40phox, p47phox, and Rac), which are recruited to the cell membranes under cell activation. All the components studied herein are represented in bold type. The established interactions based on the work reported here are represented by solid lines, whereas those that are incompletely characterized are represented by dashed lines. p40phox phosphorylation and ROI production in IgG-K. pneumoniae-stimulated AMs are regulated by a hierarchical cascade of kinases. PKCδ is rapidly activated, and this controls the subsequent activation of PAK and finally class I PI3K/Akt1. PAK itself activated ERK. p38 MAPK is activated by PKCδ. However, MAPKs do not participate in activating p40phox. Endogenous PGE₂ inhibits AM p40phox activation via the second messenger cAMP acting via unanchored PKA type II to inhibit the distal kinases PI3K/Akt. No effort was made to represent the actual localization of each kinase in the cells. P, phospho; AC, adenylyl cyclase.